Saprolegniosis are one of the most important oomycetes affecting freshwater fish worldwide. It leads to huge losses in fish farms due to their massive destruction to the fish epidermis leading to sever heamodilution and death, yet little literature studied the oxidative stress response regarding the saprolegniosis. Nile tilapia fish were subcutaneously abraded and divided into four groups: control group, abraded but not challenged, infected group, challenged with Saprolegnia. ferax (S. ferax) zoospores 2 × 104 for one week, potassium permanganate (KMnO4) group, challenged with S. ferax zoospores 2 × 104 for one week then treated with KMnO4 and lasted for 2 weeks after, Freund’s complete adjuvant (FCA) group challenged with S. ferax zoospores 2 × 104 for one week then treated with FCA and lasted for 2 weeks after and control positive group, challenged with S. ferax zoospores 2 × 104 for 3 weeks. Higher mortalities were recovered from the challenged group, which declined upon treatment compared to the continued increased rate in the control positive group. Oxidative stress indicators Nitric Oxide (NO), glutathione (GSH) and superoxide dismutase (SOD) were measured; biochemical parameters: total protein, albumin, globulin, aspartate aminotranseferase (AST), and alanine aminoranferase (ALT) were also measured. Sodium (Na+) and potassium (K+) levels were measured as indicators of Plasma osmolality. Almost of the measured parameters showed varying reduction significant levels in treatment groups compared with the infected and the control ones. Thus, this study revealed that KMnO4 have a protective role against oxidative stress response, furthermore our data provide evidence for the role of FCA in modulating the oxidative stress response and enhancing fish immune response against infections.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-94) contains supplementary material, which is available to authorized users.